Genetically Based Atrial Fibrillation: Current Considerations for
Diagnosis and Management
Abstract
Atrial fibrillation (AF) is the most common atrial arrhythmia and is
subcategorized into numerous clinical phenotypes. Given its
heterogeneity, investigations into the genetic mechanisms underlying AF
have been pursued in recent decades, with predominant analyses focusing
on early onset or lone AF. Linkage analyses, genome wide association
studies (GWAS), and single gene analyses have led to the identification
of rare and common genetic variants associated with AF risk. Significant
overlap with genetic variants implicated in dilated cardiomyopathy
syndromes, including truncating variants of the sarcomere protein titin,
have been identified through these analyses, in addition to other genes
associated with cardiac structure and function. Despite this, widespread
utilization of genetic testing in AF remains hindered by the unclear
impact of genetic risk identification on clinical outcomes and the high
prevalence of variants of unknown significance (VUS). However, genetic
testing is a reasonable option for patients with early onset AF and in
those with significant family history of arrhythmia. While many
knowledge gaps remain, emerging data support genotyping to inform
selection of AF therapeutics. In this review we highlight the current
understanding of the complex genetic basis of AF and explore the overlap
of AF with inherited cardiomyopathy syndromes. We propose a set of
criteria for clinical genetic testing in AF patients and outline future
steps for the integration of genetics into AF care.